Exome data reanalysis solved case in undetermined nephropathy with detection of TULP3-truncating variant

Chronic kidney disease (CKD) is a public health problem. In a large national registry, 20%–25% of patients with end-stage kidney disease have been reported with an undetermined kidney disease (UKD) [1–3]. Monogenic disease–causing variants are underdiagnosed in patients with CKD, with a prevalence estimation of about 10% [4]. Since 2019, we have proposed exome sequencing (ES) by next-generation sequencing to all patients with UKD. Our strategy is based on an in silico panel analysis of known genes related to kidney disease. We conducted a literature survey to add new published genes to our bioinformatics panel. We reanalyzed all ES-unsolved cases in the light of the newly discovered gene. Recently, Devane et al. [5] reported TUPL3 as a new ciliopathy-associated disease gene. Here, we report two cases that were initially described as ES-unsolved cases last year but that were in fact carriers of TULP3 pathogenic variations. One case carried the same TULP3 pathogenic homozygote variation described by Devane and colleagues and the other carried two new pathogenic biallelic variations which to our knowledge have never been described before in TULP3.